Granted Patent
B2
US 12,624,385 · App. 17/784,899 · Granted May 12, 2026
Riboregulators and methods of use thereof
Inventors:
Luis Ruben Soenksen Martinez (Boston, MA); Nicolaas Angenent-Mari (Somerville, MA); Alexander S. Garruss (Cambridge, MA); James J. Collins (Newton, MA); George M. Church (Cambridge, MA); Katherine Collins (Cambridge, MA); Diogo M. Camacho (Cambridge, MA)
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Abstract
This disclosure provides riboregulators specific for particular viruses or for particular human transcription factors. The viral-specific riboregulators may be used to detect the presence of the particular virus, and this may enable diagnosis of an infection. The transcription factor specific riboregulators may be used to detect the presence and/or measure the level of the particular transcription factor, and this may enable diagnosis or prognosis of a particular condition such as cancer.
Claims (54)
1 . A toehold riboregulator having:
(a) a nucleic acid sequence comprising any one of SEQ ID NOs: 43841, 9602, 62866, 19367, 164989, 111698, and 236638, or
(b) nucleotides 21-103 of any one of SEQ ID NOs: 43841, 9602, 62866, 19367, 164989, 111698, and 236638, or
(c) nucleotides 21-100 of any one of SEQ ID NOs: 43841, 9602, 62866, 19367, 164989, 111698, and 236638, or
(d) RNA versions of (a), (b) or (c).
2 . The toehold riboregulator of claim 1 , comprising any one of SEQ ID NOs: 43841, 9602, 62866, and 19367, or RNA versions thereof.
3 . The toehold riboregulator of claim 1 , having;
(a) a nucleic acid sequence comprising SEQ ID NO: 9602, or
(b) nucleotides 21-103 of SEQ ID NO: 9602, or
(c) nucleotides 21-100 of SEQ ID NO: 9602, or
(d) RNA versions of (a), (b) or (c).
4 . The toehold riboregulator of claim 1 , having:
(a) a nucleic acid sequence comprising SEQ ID NO: 19367, or
(b) nucleotides 21-103 of SEQ ID NO: 19367, or
(c) nucleotides 21-100 of SEQ ID NO: 19367, or
(d) RNA versions of (a), (b) or (c).
5 . The toehold riboregulator of claim 1 , having:
(a) a nucleic acid sequence comprising SEQ ID NO: 164989, or
(b) nucleotides 21-103 of SEQ ID NO: 164989, or
(c) nucleotides 21-100 of SEQ ID NO: 164989, or
(d) RNA versions of (a), (b) or (c).
6 . The toehold riboregulator of claim 1 , having:
(a) a nucleic acid sequence comprising SEQ ID NO: 111698, or
(b) nucleotides 21-103 of SEQ ID NO: 111698, or
(c) nucleotides 21-100 of SEQ ID NO: 111698, or
(d) RNA versions of (a), (b) or (c).
7 . The toehold riboregulator of claim 1 , having:
(a) a nucleic acid sequence comprising SEQ ID NO: 236638, or
(b) nucleotides 21-103 of SEQ ID NO: 236638, or
(c) nucleotides 21-100 of SEQ ID NO: 236638, or
(d) RNA versions of (a), (b) or (c).
8 . The toehold riboregulator of claim 1 covalently attached, at its 3′ end, to a nucleic acid encoding a reporter protein or reporter RNA.
9 . The toehold riboregulator of claim 1 , wherein the toehold riboregulator is specific for dengue virus, human rhino virus, or smallpox virus.
10 . The toehold riboregulator of claim 1 , wherein the toehold riboregulator is specific for a human mRNA encoding a transcription factor selected from E2F3, NCOR1, or ZNF175.
11 . A method comprising:
contacting a sample with a toehold riboregulator of claim 1 , covalently attached, at its 3′ end, to a nucleic acid encoding a reporter protein or reporter RNA, under conditions sufficient to allow the toehold riboregulator to hybridize to its respective trigger nucleic acid, and
detecting and optionally measuring expression of the reporter protein or reporter RNA,
wherein the toehold riboregulator is an RNA.
12 . The method of claim 11 , wherein the sample is obtained from a human subject.
13 . The method of claim 12 , wherein the subject is suspected of having cancer.
14 . The method of claim 12 , wherein the subject is suspected of having a viral infection.
15 . The method of claim 11 , wherein the toehold riboregulator comprises an RNA version of any one of SEQ ID NOs: 43841, 9602, 62866, and 19367.
16 . The method of claim 11 , wherein the toehold riboregulator is a plurality of toehold riboregulators comprising RNA versions of SEQ ID NO: 43841 and SEQ ID NO: 62866.
17 . The method of claim 11 , wherein the subject is suspected of having a smallpox virus infection or having been exposed to smallpox virus.
18 . The method of claim 11 , wherein the subject is suspected of having dengue virus infection or having been exposed to dengue virus.
19 . The method of claim 11 , wherein the subject is suspected of having human rhino virus infection or having been exposed to human rhino virus.
20 . The method of claim 11 , wherein the sample has been treated to amplify RNA prior to contact with the toehold riboregulator.
21 . The method of claim 20 , wherein the sample has been treated to amplify RNA isothermally prior to contact with the toehold riboregulator.
22 . A plurality of toehold riboregulators comprising a toehold riboregulator comprising SEQ ID NO: 43841 and a toehold riboregulator comprising SEQ ID NO: 62866, or RNA versions thereof.
23 . A plurality of toehold riboregulators, each comprising:
(a) a nucleic acid sequence comprising SEQ ID NO: 43841 or SEQ ID NO: 62866, or
(b) nucleotides 21-103 of SEQ ID NO: 43841 or SEQ ID NO: 62866, or
(c) nucleotides 21-100 of SEQ ID NO: 43841 or SEQ ID NO: 62866, or
(d) RNA versions of (a), (b) or (c).
Assignments (3)
CONFIRMATORY LICENSE
Recorded May 9, 2023
From: HARVARD UNIVERSITY
To: UNITED STATES DEPARTMENT OF ENERGY
Reel/Frame 063580/0772 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Sep 12, 2022
From: GARRUSS, ALEXANDER S.; CHURCH, GEORGE M.; CAMACHO, DIOGO M.
To: PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Reel/Frame 061060/0428 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Sep 12, 2022
From: MARTINEZ, LUIS SOENKSEN; ANGENENT-MARI, NICOLAAS; COLLINS, JAMES J.; COLLINS, KATHERINE
To: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Reel/Frame 061409/0331 →
Continuity (2)
Provisional Application
62948175
· Dec 13, 2019
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